DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for Coronary Restenosis — screening already-approved drugs against its 13-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCoronary Restenosis maps to a 13-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for coronary restenosis is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
FKBP prolyl isomerase 1A (FKBP1A) — FKBP1A is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet 4~{s},5~{r},6~{z},9~{s},10~{s},12~{e}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6I1S · 1.52 Å · ligand (4~{S},5~{R},6~{Z},9~{S},10~{S},12~{E})-16-(ethylamino)-4,5-dimethyl-9,10,18-tris(oxidanyl)-3-oxabicyclo[12.4.0]octadeca-1(14),6,12,15,17-pentaene-2,8-dione (E26). Experimental structure, not a prediction.
What the evidence adds up to
A genome-wide association study of 295 restenosis cases and 571 matched controls from the GENDER databank tested 54 biological pathways related to inflammation, proliferation, vascular function and transcriptional regulation. Six pathways showed nominal significance in one or two of three software packages, but only two SNPs in the cell-extracellular matrix interactions pathway replicated in an independent cohort. No replication was obtained for the other five pathways. The authors describe this as a hypothesis-generating effort for further functional studies.
A 2001 review argues that enthusiasm for gene therapy in coronary restenosis is not yet justified. It notes that 16–32% of selected trial patients develop restenosis within six months, requiring target vessel revascularisation in 9–15%. The review states that conventional pharmacological agents have failed to inhibit restenosis and that current understanding of human restenosis pathogenesis is insufficient to know which genetic material to deliver, nor how to deliver it effectively and safely. It emphasises that animal vascular injury models do not reliably reproduce the human response to percutaneous coronary intervention.
A Swedish registry study of 6642 clinically defined restenosis episodes in 2978 patients between 1995 and 2005 found that only 39.7% presented as stable angina. The majority presented as acute coronary syndrome: 46.0% as unstable angina or non-STEMI, 11.5% as STEMI, and 2.8% as other reasons. Cardiogenic shock occurred in 48 patients. Mortality was 1.7% at 30 days, 3.2% at six months, and 4.6% at one year. STEMI was less frequent after drug-eluting stents (7.9%) than after bare metal stents (18.5%), and less frequent after balloon angioplasty (6.9%) than after in-stent restenosis (13.8%). Women had more unstable angina (52.3% vs 43.6%) but less STEMI (9.6% vs 12.2%).
A 2025 study of 181 patients (67 with restenosis, 114 without) found restenosis was more common in men (82.1% vs 69.3%, p=0.047). After propensity score matching for sex, the restenosis group had higher hereditary cardiovascular predisposition (p=0.024), higher prevalence of sinus rhythm (p=0.020), lower serum apolipoprotein A1 (p=0.048), and higher alanine aminotransferase (p=0.023). No trial has yet shown that modifying any of these factors reduces restenosis. What is missing is a proven molecular target, a safe and efficient delivery method for local gene therapy, and prospective randomised evidence that any identified biomarker or pathway can be therapeutically exploited to change clinical outcomes.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PLoS ONE · 2013 · 15 citations · open access
Pathway Analysis Using Genome-Wide Association Study Data for Coronary Restenosis – A Potential Role for the PARVB Gene
AbstractBACKGROUND: Coronary restenosis after percutaneous coronary intervention (PCI) still remains a significant limitation of the procedure. The causative mechanisms of restenosis have not yet been fully identified. The goal of the current study was to perform gene-set analysis of biological pathways related to inflammation, proliferation, vascular function and transcriptional regulation on coronary restenosis to identify novel genes and pathways related to this condition. METHODS: The GENetic DEterminants of Restenosis (GENDER) databank contains genotypic data of 556,099SNPs of 295 cases with restenosis and 571 matched controls. Fifty-four pathways, related to known restenosis-related processes, were selected. Gene-set analysis was performed using PLINK, GRASS and ALIGATOR software. Pathways with a p<0.01 were fine-mapped and significantly associated SNPs were analyzed in an independent replication cohort. RESULTS: Six pathways (cell-extracellular matrix (ECM) interactions pathway, IL2 signaling pathway, IL6 signaling pathway, platelet derived growth factor pathway, vitamin D receptor pathway and the mitochondria pathway) were significantly associated in one or two of the software packages. Two SNPs in the cell-ECM interactions pathway were replicated in an independent restenosis cohort. No replication was obtained for the other pathways. CONCLUSION: With these results we demonstrate a potential role of the cell-ECM interactions pathway in the development of coronary restenosis. These findings contribute to the increasing knowledge of the genetic etiology of restenosis formation and could serve as a hypothesis-generating effort for further functional studies.
Gene therapy for coronary restenosis: is the enthusiasm justified?
AbstractDespite dramatic technological advances in coronary intervention, restenosis following percutaneous coronary intervention remains an important cause of morbidity with major financial implications.1 By six months postprocedure, some 16–32% of highly selected patients receiving optimal treatment within the privileged context of a clinical trial have developed restenosis, necessitating target vessel revascularisation in 9–15% of patients. The development of antirestenotic treatments is therefore an area of intense research activity. The failure of conventional pharmacological agents to inhibit restenosis, along with concern over the long term safety and efficacy of intracoronary brachytherapy, has fostered the belief that gene therapy may be the future of antirestenotic treatments.2 3 Furthermore, the focal nature of restenosis makes it a highly attractive target for locally delivered genetic material that may have toxic effects if administered systemically. However, the important question remains: can research in this field translate into clinically useful treatment or is our enthusiasm for antirestenotic gene therapy misplaced?
There are two fundamental questions that must be answered before antirestenotic gene therapy may become a reality. Firstly, what genetic material should be delivered? We believe that current understanding of the pathogenesis of human restenosis is insufficient to allow us to answer this question confidently. Secondly, and equally important, how should genetic material be delivered effectively and safely?
### DIFFERENCES BETWEEN ANIMALS AND HUMANS
Many of the proposed targets for antirestenotic gene therapy have arisen from study of the effects of vascular injury in animals. Myriad papers report delivery of various transgenes that suppress the response to experimental vascular injury. This often leads to the postulate that a similar strategy would limit human restenosis. However, for such “gene therapies” to be useful in humans, the animal vascular injury and human percutaneous coronary intervention must produce similar physical insult to the vascular wall and provoke a similar injury response. Unfortunately, we cannot …
Abstract 5609: In-Stent Restenosis - Benign or Dangerous? Clinical Presentation of Coronary Restenosis in Sweden
AbstractBackground Restenosis after percutaneous coronary intervention (PCI) was earlier thought to be a benign event clinically manifested as stable exertional angina. The aim of this prospective multicenter registry study was to investigate the incidence of acute coronary syndrome in patients with restenosis in Sweden. Methods Using data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), we analyzed all registered cases of PCI for restenosis (in-stent, after balloon angioplasty) from 1995 to 2005 in Sweden. Both multivessel and single vessel interventions were included. Restenosis presentations were classified as: stable angina; unstable angina/non-STEMI; STEMI; and other reasons. As routine angiographic screening was not performed, restenosis episodes were defined clinically based on symptoms. Results We identified 6642 cases of restenosis in 2978 patients (4790 in men, 1852 in women). Restenosis presented in 39.7% of cases as stable angina, in 46.0% as unstable angina/non-STEMI, in 11.5% as STEMI and in 2.8% as other reasons. Cardiogenic shock was reported in 48 patients. Women had a higher incidence of unstable angina/non-STEMI compared with men (52.3% v. 43.6%) but a lower incidence of STEMI (9.6% v. 12.2%). The frequency of STEMI was lower with restenosis after balloon angioplasty v. in-stent restenosis (6.9% v. 13.8%), and after drug-eluting stents v. bare metal stents (7.9% v. 18.5%). Mortality rate was 1.7% at 30 days, 3.2% at 6 months and 4.6% at one year in patients with restenosis. These covariates were independent predictors of acute coronary syndrome: gender, age, vessel diameter, smoking, stent type, number of stents, treated vessel, previous stroke and previous infarction. Conclusion The majority of patients with coronary restenosis present either with acute MI or unstable angina requiring hospitalization and new interventions. Women may have a higher risk of developing acute coronary syndrome due to restenosis. Prevention of restenosis may be an important target for improvement of “hard” clinical outcomes in patients undergoing coronary revascularization.
Russian Journal of Cardiology · 2025 · 0 citations · open access
Clinical and serum risk factors for coronary restenosis in patients with coronary artery disease
AbstractAim. To study risk factors for coronary artery restenosis in a retrospective (identification of patients with restenosis) and prospective (biomarker analysis) study. Material and methods. Patients with coronary stenosis were identified within 7 years after primary stenting. In 181 patients (67 — with coronary restenosis, 114 — without coronary restenosis), the clinical, demographic and serum biomarker profiles of patients were studied. Results. The incidence of coronary restenosis was significantly higher in men (82,1% and 69,3%, p=0,047). Propensity score matching was used to balance the groups by sex, and as a result, a higher hereditary predisposition to cardiovascular diseases (p=0,024), sinus rhythm (p=0,020), low serum apolipoprotein A1 (p=0,048) and high alanine aminotransferase (p=0,023) were shown for the restenosis group. Conclusion. Coronary artery restenosis was characterized by male sex, sinus rhythm, hereditary predisposition, increased alanine aminotransferase and decreased apolipoprotein A1.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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